ASH2010慢性髓性白血病12-10-2
慢性髓性白血病研究进展-第52届ASH会议重点解读 December 4-7, 2010 Orlando, FL 山东大学齐鲁医院纪春岩 2010-12-12(济南)第52届ASH会议慢性髓性白血病相关文献AbstractsLate breaking AbstractsOral and Poster AbstractsChronic Myeloid Leukemia - TherapyChronic Myeloid Leukemia - Biology and PathophysiologyEducation ProgramCML 2010: Where Are We Now and Where Can We Go?第一部分 CML治疗-TKI 伊马替尼 比较大剂量与标准剂量伊马替尼治疗的有效性及安全性 (the German CML-Study IV) 分析伊马替尼治疗的分子反应程度与生存的关系 评估伊马替尼治疗老年患者的疗效及安全性 评价伊马替尼治疗青少年患者的临床疗效 尼洛替尼 评估尼洛替尼治疗的有效性和安全性(ENESTnd Trial) 达沙替尼 评价达沙替尼治疗的有效性和安全性(DASISION Trial) 比较达沙替尼和伊马替尼治疗的有效性和安全性 (The S0325 Intergroup Trial) 分析BCR-ABL激酶区突变与治疗反应的关系Oral and Poster Abstracts Late-breaking AbstractsSeven-YearFollow-upDataonSequentialProspectiveTrialsofImatinib400mgVs800mgDailyScheduleforFront-LineTreatmentofChronicMyeloidLeukemia(CML)Naveen Pemmaraju, MD Poster Session: Chronic Myeloid Leukemia - Therapy: Poster III 3438目的-比较使用伊马替尼800mg与400mg作为CML一线治疗的长期临床疗效结果IM800mg(n=208)IM400mg(n=73)P值中位随访时间mos(范围)79(3-107)110(2-116)-累积CCyR率91%87%0.49累积MMR率87%78%0.0612 个月CCyR90%66%0.001*18个月MMR82%68%0.04*7年EFS 86% 76%0.049*7年TFS-0.467年OS-0.27因毒性中止治疗16(8%)6(8%)-Seven-YearFollow-upDataonSequentialProspectiveTrialsofImatinib400mgVs800mgDailyScheduleforFront-LineTreatmentofChronicMyeloidLeukemia(CML)Naveen Pemmaraju, MD Poster Session: Chronic Myeloid Leukemia - Therapy: Poster III 3438结论-7年跟踪调查显示:与伊马替尼400mg相比,伊马替尼800mg 12 个月CCyR 、18个月MMR、7年PFS明显改善,但OS无差异-大剂量伊马替尼治疗CML有一定益处SuperiorCMR-RateswithTolerability-AdaptedImatinib800MgVs.400MgVs.400Mg+IFNInCML:TheRandomizedGermanCML-StudyIVRdiger Hehlmann, MD Oral Session: Chronic Myeloid Leukemia - Therapy: Optimizing Front-Line Therapy in CML 357 目的-评价大剂量伊马替尼治疗初诊Ph+ CML-CP患者的疗效 研究设计-完全分子学缓解CMR被定义为BCR-ABL/ABLIS 0.01%-1012例CML患者入组(338例IM 800mg;324例IM 400mg;350例IM联合干扰素)-IM 800mg组,平均每日伊马替尼剂量628mg;IM 400mg组,平均每日伊马替尼剂量400mgRdiger Hehlmann, MD Oral Session: Chronic Myeloid Leukemia - Therapy: Optimizing Front-Line Therapy in CML 357 结果-IM 800mg组12个月缓解率显著提高 12个月累积CCyR:IM 800mg组为63%;IM 400mg及联合组为50% 12个月累积MMR:IM 800mg组为54.8%;IM 400mg组为30.8%; 联合组为34.7% 36个月内IM 800mg组均有较高的CMR,且比IM 400mg组更快获得CMR初始治疗时间(月)累积发病率MMR(%)CMR(%)IM400n=306IM800n=328IM400+IFNn=336IM400n=306IM800n=328IM400+IFNn=33668.618.18.43 3.7 2.4 12 30.8 54.8 34.7 7.5 19.8 12.4 1850.368.454.121.2 33.4 23.6 246376.062.830.7 43 30.0 3679.381.670.745.5 56.8 40.5 SuperiorCMR-RateswithTolerability-AdaptedImatinib800MgVs.400MgVs.400Mg+IFNInCML:TheRandomizedGermanCML-StudyIVSuperiorCMR-RateswithTolerability-AdaptedImatinib800MgVs.400MgVs.400Mg+IFNInCML:TheRandomizedGermanCML-StudyIV Rdiger Hehlmann, MD Oral Session: Chronic Myeloid Leukemia - Therapy: Optimizing Front-Line Therapy in CML 357 结论-大剂量伊马替尼治疗耐受性良好-伊马替尼800mg组比400mg组获得更高CMR-伊马替尼800mg组比400mg组有更多患者获得稳定CMR MolecularResponse1%BCR-ABLISat12MonthsIsAssociatedwithImprovedOverallandProgression-FreeSurvival:theRandomizedGermanCML-StudyIVMartin C. Mller, MD Oral Session: Chronic Myeloid Leukemia - Therapy: Rethinking Therapy Targets and Prognostic Factors 669 目的-评估分子反应程度与生存的关系 研究设计-848例CML患者入组-3个分子反应组 (1% BCR-ABL/ABLIS) -12个月PFS和OS 结果-12个月时,341例患者获得MMR(BCR-ABL/ABLIS1%-与BCR-ABL/ABLIS 1%组相比, BCR-ABL/ABLIS 0.1%-1%和MMR组3年PFS和OS更高Martin C. Mller, MD Oral Session: Chronic Myeloid Leukemia - Therapy: Rethinking Therapy Targets and Prognostic Factors 669 结论-更快、更深的分子反应与PFS和OS的提高有关-关键临界值似乎是1% BCR-ABL/ABLIS水平(与CCyR密切相关)MolecularResponse65years):ResultsoftheGermanCML-StudyIVSusanne Saussele, MD Poster Session: Chronic Myeloid Leukemia - Therapy: Poster III 3411 目的-评估伊马替尼治疗年龄大于65岁CML患者的疗效及安全性 研究设计-以65岁为年龄分界,分为IM 400mg和800mg组-观测血液学、细胞遗传学、分子学缓解时间,总生存率和不良反应年龄65(n=150)65years):ResultsoftheGermanCML-StudyIVSusanne Saussele, MD Poster Session: Chronic Myeloid Leukemia - Therapy: Poster III 3411 结果 有效性-年老与年轻患者间细胞遗传学和分子学缓解率无显著差异-IM 400mg组中,年老比年轻患者更慢获得CCyR和MMR(CCvR: 14.2 月 vs 12.1 月,p=.019; MMR: 18.7 月 vs 17.5 月,p=.006)-IM 800mg组中,两组间无差异 (CCvR : 7.7 月 vs 8.9 月, MMR: 9.9 月 vs 10.0 月)-3年总生存率两组分别为94.7% 和96.1% 安全性-血液学不良反应:年老比年轻患者稍重-3、4级非血液学不良反应:无差异TherapywithImatinibInElderlyCMLPatients(65years):ResultsoftheGermanCML-StudyIVSusanne Saussele, MD Poster Session: Chronic Myeloid Leukemia - Therapy: Poster III 3411 结论-年老患者使用伊马替尼400mg和800mg均耐受性良好-应用伊马替尼800mg治疗,年老与年轻患者获得CCyR和MMR的中位时间无差异-应用伊马替尼400mg治疗,年老患者比年轻患者更慢获得CCyR和MMRAnalysisofOutcomesInAdolescentsandYoungAdults(AYA)withChronicMyeloidLeukemia(CML)TreatedwithUpfrontTyrosineKinaseInhibitors(TKI)Naveen Pemmaraju, MD Poster Session: Chronic Myeloid Leukemia - Therapy: Poster 1234 目的-评价酪氨酸激酶抑制剂治疗青少年CML患者的临床疗效 研究对象-年龄15至21岁的CML患者;移植患者排除 结果年龄21(n=422)P 值总数Sokal危险度,n(%)低危中危高危12(92)1(8)0288(68)105(25)29(7)0.24300(69)106(24)29(7)CCyR, n (%) 7 (64) 384 (93) 0.008 391/425中位达CCyR时间(月)333(2-64)MMR,n(%)7(64)359(87)0.0497366/424中位达MMR时间(月)966(2-78)CMR,n(%)1(9)160(39)0.06161/424中位达CMR时间(月)122424(3-84)5年无事件生存79900.265年无进展生存(%)100940.515年总生存(%)88930.9AnalysisofOutcomesInAdolescentsandYoungAdults(AYA)withChronicMyeloidLeukemia(CML)TreatedwithUpfrontTyrosineKinaseInhibitors(TKI)Naveen Pemmaraju, MD Poster Session: Chronic Myeloid Leukemia - Therapy: Post